Understanding inborn errors of immunity: A lens into the pathophysiology of monogenic inflammatory bowel disease.
Understanding inborn errors of immunity: A lens into the pathophysiology of monogenic inflammatory bowel disease.
复制标题
DOI：
10.3389/fimmu.2022.1026511
复制
发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
炎症性肠病（IBD）是胃肠道的慢性炎症性疾病，包括克罗恩病、溃疡性结肠炎和炎症性肠病（IBD- u）。IBD被认为是多因素的，涉及遗传、免疫、微生物和环境因素。新一代测序技术的进步有助于越来越多地确定IBD的80多种单基因病因，其中许多与先天性免疫错误（IEI）重叠；目前确定的IEI中约有三分之一会导致胃肠道表现，其中许多是炎症性的，如IBD。事实上，胃肠道是研究IEI的一个合适的系统，因为它由体内最大的淋巴组织组成，并利用一层薄薄的肠上皮细胞作为肠腔和宿主之间的关键屏障。在这篇小型综述中，我们描述了一系列导致单基因IBD的相关IEI，包括肠上皮屏障、吞噬、T细胞和B细胞缺陷以及那些损害中枢和外周耐受性的疾病。在肠道疾病患者中，肠道-微生物-宿主相互作用的破坏在扰乱肠道稳态中的作用也被讨论。分子机制驱动的发病机制，以及个性化的治疗干预和研究途径，这些不断增长的知识使之成为可能。
Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract, including Crohn’s disease, ulcerative colitis and inflammatory bowel disease-undefined (IBD-U). IBD are understood to be multifactorial, involving genetic, immune, microbial and environmental factors. Advances in next generation sequencing facilitated the growing identification of over 80 monogenic causes of IBD, many of which overlap with Inborn errors of immunity (IEI); Approximately a third of currently identified IEI result in gastrointestinal manifestations, many of which are inflammatory in nature, such as IBD. Indeed, the gastrointestinal tract represents an opportune system to study IEI as it consists of the largest mass of lymphoid tissue in the body and employs a thin layer of intestinal epithelial cells as the critical barrier between the intestinal lumen and the host. In this mini-review, a selection of pertinent IEI resulting in monogenic IBD is described involving disorders in the intestinal epithelial barrier, phagocytosis, T and B cell defects, as well as those impairing central and peripheral tolerance. The contribution of disrupted gut-microbiota-host interactions in disturbing intestinal homeostasis among patients with intestinal disease is also discussed. The molecular mechanisms driving pathogenesis are reviewed along with the personalized therapeutic interventions and investigational avenues this growing knowledge has enabled.